There are two objectives of this project: The first is to delineate, describe and analyze the major factors determining and/or regulating the cellular acid-base state of frog skeletal muscles so that the role of cells in the overall acid-base regulatory processes of the body can be better understood. The second objective is to develop a detailed, quantitative description of the permeation of anions (including HCO3) through anion channels of the membrane under a variety of conditions and thereby deduce much detail about the essential molecular structures of the channel. These objectives are congenial because detailed knowledge of the determinants of HCO3 permeation is necessary for calculating passive HCO3 fluxes and the counterbalancing active fluxes. The experimental approaches are much the same for both objectives: (1) Voltage-clamping techniques will be used to measure anion fluxes, equilibrium potentials, and the time and voltage dependences of anion conductance. (2) Radioisotope tracer, intracellular ion selective electrodes and voltage-clamping techniques will be used in an attempt to determine the dependence of anion conductances on intracellular pH and the nature and limits of pH regulation by cells. (3) Use of intracellular chloride-ion electrodes to follow the time course of changes in chloride-ion activity in acid-base disturbances, which probably reflect complementary changes in internal (HCO3). This research has clinically important implications: (1) The acid-base interactions between cells and extracellular fluid must be understood in order to make the diagnosis of acid-base disorders more precise. (2) The acid-base state of the cell interior is probably as important as that of extracellular fluid in determining overall bodily response to acid-base alterations. Hence, better diagnosis and treatment require knowledge of these processes.